Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model.
Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model.
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DOI：
10.1016/j.stemcr.2015.11.008
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发表时间：
2016-01-12
影响因子：
5.9
通讯作者：
Kvanta A
中科院分区：
文献类型：
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作者：
Plaza Reyes A;Petrus-Reurer S;Antonsson L;Stenfelt S;Bartuma H;Panula S;Mader T;Douagi I;André H;Hovatta O;Lanner F;Kvanta A
人胚胎干细胞（hESC）衍生的视网膜色素上皮（RPE）细胞可以替代地图状萎缩（GA）中丢失的组织，但疗效尚未在大眼模型中得到证实。此外，hESC-RPE的生产尚未以无异种和确定的方式实现，这对于临床依从性和降低免疫原性至关重要。在这里，我们描述了一种有效的分化方法，使用人层粘连蛋白-521基质与异种和确定的培养基。分化的细胞表现出天然RPE的特征，包括形态、色素沉着、标记物表达、单层完整性、极化以及吞噬活性。此外，我们建立了一个大眼睛的GA模型，允许在体内成像的hESC-RPE和宿主视网膜。悬浮移植的细胞表现出长期的整合，并形成极化的单层表现出吞噬和光感受器救援能力。我们已经开发了一种无异种和定义的hESC-RPE分化方法，并提出了在大眼疾病模型中临床顺应性hESC-RPE功能整合的证据。使用重组层粘连蛋白-521基质的hES-RPE细胞的无异种和确定的分化在新的大眼疾病模型中hES-RPE细胞的功能性单层整合通过移植的hES-RPE细胞将光感受器从诱导的变性中拯救Lanner和同事提出了一种使用重组人层粘连蛋白-521基质的有效的无异种和确定的hES-RPE细胞分化方法。他们进一步提出了在大眼疾病模型中移植hES-RPE细胞的长期功能整合和光感受器拯救的证据。
Human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells could replace lost tissue in geographic atrophy (GA) but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model. Xeno-free and defined differentiation of hES-RPE cells using recombinant laminin-521 Functional monolayer integration of hES-RPE cells in a novel large-eyed disease model Rescue of photoreceptors from induced degeneration by transplanted hES-RPE cells Lanner and colleagues present an effective xeno-free and defined hES-RPE cell differentiation methodology using a recombinant human laminin-521 matrix. They further present evidence of long-term functional integration and photoreceptor rescue by transplanted hES-RPE cells in a large-eyed disease model.